DESCRIPTION: (Adapted from the application): The goal of this proposal is to understand spinal cord mechanisms that regulate sympathetic activity, with special attention to the roles of these mechanisms after spinal cord injury. In patients with severe spinal cord injury, ordinarily innocuous stimuli, such as a full bladder, can lead to paroxysmal increases in the activity of the sympathetic nervous system. These inappropriate sympathetic responses can lead to hypertensive crises that result in seizures or stroke. Few methods have been available for studying the spinal mechanisms that generate sympathetic activity. Recently, however, we have adapted to the spinal cord the classical neurophysiological technique of spike triggered averaging that has been successfully used to study brainstem generators of sympathetic nerve activity. In addition, we conduct all of our experiments in anesthetized rats, which, unlike most experimental animals do not suffer profound autonomic spinal shock after spinal transection. Some of their sympathetic nerves exhibit normal, or even elevated, levels of activity within minutes of transection. The proposed experiments will accomplish 3 aims. In Aim I, working in cervically transected anesthetized rats, we will determine the role(s) of spinal interneurons in generating excitation or inhibition of renal sympathetic nerve activity. These experiments will elucidate the intraspinal neurons and pathways that may be responsible for generating dysfunctional sympathetic activity after spinal injury. In Aim II, we will determine whether these same neurons are important for generating or conveying excitation and inhibition of renal sympathetic nerve activity in spinally-intact rats. These experiments will help us understand the normal sympathetic roles of spinal interneurons and their results will be useful in developing physiological methods for preventing hypertensive crises. Finally, in Aim III, we will determine the role of rostral, cervical spinal cord neurons in the regulation of sympathetic activity in spinally-transected and intact rats. Studies from this laboratory suggest a sympathoinhibitory role for this region and an understanding of this role may lead to better treatments for abnormal sympathetic activity after spinal cord injury.